Project Abstract Ischemic stroke is a potentially preventable, devastating complication of sickle cell disease (SCD), a group of inherited blood disorders that affect close to 100,000 individuals in the United States. Without intervention, stroke may occur in up to 24% of individuals with the highest risk form of SCD, sickle cell anemia. Despite improvements in comprehensive care and management of SCD in children, stroke remains a major cause of morbidity and mortality due to insufficient screening and prevention practices. Individuals living with SCD continue to face multiple health disparities cause by racial and socioeconomic factors as well as disease- specific disparities in funding and private sector support. In order to standardize and improve care, the National Heart, Lung, and Blood Institute (NHLBI) released evidence-based guidelines in 2014. These guidelines established routine transcranial Doppler ultrasound (TCD) screening as a means for identifying children at high risk of stroke and indefinite chronic red cell transfusions (CRCT) as a means of treating children at high risk for stroke based on the previous NHLBI funded, randomized controlled STOP (Stroke Prevention Trial in Sickle Cell Disease) results. This proposal, entitled DISPLACE (Dissemination and Implementation of Stroke Prevention Looking at the Care Environment) is a multi-site effort focused on enhancing the implementation and dissemination of these evidence-based stroke prevention guidelines in SCD. The research approach is guided by the Interactive Systems Framework for Dissemination and Implementation and the multilevel ecological model of health. The DISPLACE leadership core at the Medical University of South Carolina is a multidisciplinary team lead by Dr. Julie Kanter, Dr. Robert Adams and Dr. Cathy Melvin and includes specialists in multicenter clinical trial design, hematology, implementation science, qualitative analysis and statistical evaluation. The Data Coordinating Unit (DCU) at MUSC who have coordinated over 40 multicenter studies and will provide study design and information technology support and data management support the leadership core. The aims of DISPLACE are to: 1) assess the gap between current and guideline- recommended practices for stroke prevention among pediatric patients with SCD, 2) assess the multi-level patient, provider, and systems barriers and enablers to performing TCD screening and initiating CRCT, and 3) evaluate the effectiveness of a novel multi-level dissemination and implementation strategy to increase current annual TCD screening rates and CRCT initiation rates using a parallel cluster-randomized clinical trial. We have assembled a large, multi-institutional collaboration of institutions with widespread geographic distribution to best assess the feasibility and utility of the multi-level implementation strategy. The long-term goal of DISPLACE is to ensure that all children with SCD receive guideline-based care for stroke prevention for a ?stroke free generation? in SCD.